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KyleBWalshMDAssistantProfessor-UCDeptofEmergencyMedicine

FellowPhysician-NeurocriticalCare,Stroke,Research

ManagementofIschemicStrokeintheIntensiveCareUnit

WhyICUcaremattersforischemicstrokepatientsPatientCases

Toillustrate:

ComplicationsfollowingischemicstrokeSubsequenttreatments

Outline

PhasesofStrokeDiagnosisandTreatment

1.  MakingtheDiagnosis•  Variablecomplexityofpresentation

2.  DecidingaboutImmediateTreatment•  tPA,endovasculartherapy

3.  SubsequentCare•  Preventionoffurtherdamageanddeterioration

•  Treatingpotentialcomplications

•  ICUCare

Introduction

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-Howmanypatientsreceiveacutetreatment?

•  370,351acuteischemicstrokeprimarydischargediagnosis•  4%receivedtPA

•  0.5%receivedendovasculartherapy

•  Continuedeffortstoincreaseacutetreatmentrates•  Subsequentcareisimportant

StrokeTreatment

Adeoyeetal.Stroke.2014Oct;45(10):3019-24.

ICUCareMatters

•  Managementbyaneurocriticalcareteam•  Decreasedhospitallengthofstay

•  DecreasedICUlengthofstay

•  Increasedproportionofhomedischarges

NeurocriticalCare

Bershadetal.NeurocritCare.2008;9(3):287-92.

62yearoldmalewokeupwithMildrightarmweakness

Minorfacialdroop

Partialarmsensoryloss

Lastknownnormal7hourspriorNIHSS3

PastMedicalHistory:Diabetes,Hypertension,Hyperlipidemia

SocialHistory:Smoking

Case#1

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•  NotacandidatefortPAorendovasculartherapy•  CTheadshowsnohemorrhage•  Bloodpressureis210/110Whatshouldbedoneforthepatient’sbloodpressure?

Case#1

•  TreatmentthresholdBP>220/120•  Lowerthresholdforcomplications(e.g.CHF)

•  BPmustbe<185/110toqualifyfortPA•  MaintainBP<180/105for24hoursaftertPA

Manypatientswillbehypertensiveafterstroke•  SBP>139in77%and>184in15%uponarrivaltoED

Whyallowsuchahighbloodpressure?

Hypertension

Jauchetal.Stroke.2013Mar;44(3):870-947denHertogetal.LancetNeurol.20098:434–440

-Toperfusethepenumbra,theareaofbrainthatisatrisk-Impairedautoregulation,thus,dependentonsystemicBP www.radiologyassistant.nl

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•  11,080patientstreatedwithtPAfrom2002to2006

BloodPressureAftertPA

Ahmedetal.Stroke.2009Jul;40(7):2442-9.

ForadmissionBPinacuteischemicstroke:

•  SomestudieshavefoundU-shapedrelationships•  Othersreportlinearrelationships

ElevatedBPwhileinthehospital•  Moreconsistentlinearrelationshipwithpooroutcome

BloodPressureManagement

Jauchetal.Stroke.2013Mar;44(3):870-947

BPfollowingischemicstroke:•  Adynamicprocess

•  Needstobemonitoredfrequently

•  Potentialtrendsandfluctuationsthatrequireintervention

Hypotensionfollowingischemicstrokeisrare•  Studyof11,080patients:only0.6%withSBP<100

•  Oftenindicatesanothercause

•  Cardiacdysfunction,vasculardissection,shock

•  BrainisveryvulnerabletolowBPfollowingstroke

BloodPressureManagement

Ahmedetal.Stroke.2009Jul;40(7):2442-9.Jauchetal.Stroke.2013Mar;44(3):870-947

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62yearoldmalewokeupwithMildrightarmweakness

Minorfacialdroop

Partialarmsensoryloss

Lastknownnormal7hoursagoNIHSS3

Bloodpressure180/90

Case#1Revisited

Case#1Revisited

2hourslater

Worseningweaknessofrightface,arm,leg,aphasiaNIHSSincreased:3to11

Bloodpressuredecreased:180/90to130/70

Shouldthepatient’sbloodpressurebeincreased?

TherapytoincreasebloodpressureinischemicstrokeApotentialtherapyintheICUEvidencefromsmallstudies

Suggestsafetyandeffectivenessinselectpatients

Whichpatients?

PressorTherapy

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1)  PatientswithsustainedSBP<130to150mmHgORthosewithevidenceofasymptomaticBPdecrease(20mmHg)followingischemicstroke

2)  Severeipsilaterallargeextracranialorintracerebralvesselstenosisorocclusion

3)  Presentingwithin12hoursorperhaps24hoursofsymptomonset

4)  Withoutobviousexclusioncriteriatopressortherapy,

(e.g.EF<25%,recentCHF,MI,pastmedicalhistoryofarrhythmias)

PressorTherapy

Mistrietal.Stroke.2006Jun;37(6):1565-71.

•  57yoFemalefounddown•  Aphasia,rightsided

hemiplegia,Lgazepreference

•  NIHSS22

LKN:8hourprior

Case2

Case2

24hourfollow-upCT

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MalignantMCAsyndromeSomewithlargestrokeswilldeteriorateininitial24-48hours

MassiveedemaandseveremidlineshiftMalignantstrokesconstituteupto10%ofstrokes

Mortalityisashighas80%Earlyidentificationisessential

MalignantIschemicStroke

Riskfactorsformalignantcerebraledema:1)EarlyCThypodensitygreaterthan50%oftheMCAterritoryORDiffusionlesionvolumegreaterthan82mLwithin6hoursofstrokeonset2)Involvementofadjacentvascularterritories(suchasACAorPCA)

MalignantIschemicStroke

Kasneretal.Stroke.2001Sep;32(9):2117-23.

DecompressivehemicraniectomyToallowspacefortheswellingtooccur

Reducefluidshifts,pressureintheintracranialcompartment

Isitbeneficial?Pooledanalysisof3RCTs,93patients,18-60yearsold

NIHSS>15,CTwithhypodensity>50%MCA

Maximumtimeof48hoursfromstrokeonset

MalignantEdemaTreatment

Vahedietal.LancetNeurol.2007Mar;6(3):215-22.

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Outcomesat1yearfollowingstrokeMortality: 28%withsurgery,78%withoutmRS0-4: 75%withsurgery,24%without

mRS0-3: 43%withsurgery,21%without

DecompressiveHemicraniectomy

0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.

Whataboutolderpatients?112patientswithmalignantMCA

>61years,(median71,range61-82)

Outcomeat6monthsfollowingstroke:

Mortality: 33%withsurgery,70%without

mRS0-4: 38%withsurgery,18%without

mRS0-2: Nopatients

mRS3: 7%withsurgery,3%without

mRS4: 32%withsurgery,15%without

mRS5: 28%withsurgery,13%without

Juttleretal.NEnglJMed.2014Mar20;370(12):1091-100.

•  AtreatmentintheICUformalignantedemaMannitol

TypicallyadministeredasbolusesQ4to6hours

Longhistory,consideredbysometobe“goldstandard”

Hypertonicsaline

Bolusesorcontinuousinfusion

BothreduceICPthroughvariousmechanisms:Volumeredistribution,plasmaexpansion,rheologicmodifications,anti-inflammatoryeffects

HyperosmolarTherapy

Torre-Healyetal.NeurocritCare.2012Aug;17(1):117-30.

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Mannitol:

Renalfailure,electrolytedisturbances,initialplasmavolumeexpansion,hypotension,ICPrebound

Hypertonicsaline(HS):Renalfailure(lesscommon),electrolytedisturbances,centralpontinemyelinolysis,infusionphlebitis

HSoftendescribedashaving“morefavorablesideeffectprofile.”

AdverseEffects

Markoetal,CritCare.2012Feb20;16(1):113.

Mannitolvs.HS:Whichismoreeffective?Limitedevidence:

•  Inischemicstroke:

16of16episodesofincreasedICPrespondedtoHS

10of14respondedtomannitol

•  MeanICPreduction11mmHgwithHS,5mmHgwithMannitol

•  Meta-analysisof5trialsforelevatedICP(3includedstroke):ICPsuccessfullyreduced78%ofthetimewithmannitol,93%withHS

ShouldHSbethenewgoldstandard?

Schwarzetal.Stroke.1998Aug;29(8):1550-5.

Kameletal.CritCareMed.2011Mar;39(3):554-9.

•  51yearoldmale,suddenonsetofvertigo,vomiting

•  Unabletostandorwalkindependently

•  BP160/85

•  Glucose170

•  NIHSS1(ataxia)

•  Onsetofsymptoms2hoursprior,treatedwithIVtPA

Case3

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24hourrepeatCT

Case3

Case3

48hourrepeatCT

•  PosteriorcirculationstrokeCanresultinseverecomplicationsdueto:

•  Obstructivehydrocephalusfromcompressionofthe4thventricle

•  Directcompressionofthebrainstem

Withsignsofbrainstemcompression,mortalityabout80%withoutsurgery

Surgeryreducesmortality

20%forthosetreatedsurgicallyincomatosestate

Case3

Juttleretal.Stroke.2009Sep;40(9):3060-6.

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Edlowetal.LancetNeurol.2008Oct;7(10):951-64.

Monro-KellieDoctrine

ThebrainisenclosedintheskullThus,thevolumeisconstantAverageadultmale,approximately1500ml1250mlBrain150mlCerebrospinalFluid100mlBloodSomething(i.e.bloodorCSF)mustbepushedoutifpressurerises

Monro-KellieDoctrine

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TreatmentsforPosteriorCirculationStroke:

EVD:ExternalVentricularDrain

DecompressiveSurgery

MakingthediagnosisiskeyClosemonitoringintheICUsettingEarlyMRI

Involveaneurosurgeonearly

Temporizingmeasuresifindicated

Hyperosmolartherapy

ICUcarefollowingEVDplacementand/ordecompressivecraniotomy

PosteriorCirculationStrokes

72yearoldfemale,leftface/arm/legweakness,rightgazepreference,leftsidedneglect

LKN24hoursprior

NIHSS16

BP160/90

Glucose350

Case4

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ThoughttoincreasemetabolicdemandinthebrainResultsinlacticacid,variousfreeradical

Neuronalcelllysis,damagetobloodbrainbarrier

Negativeoutcomesnotedinhyperglycemicstrokepatients

•  Increasedcerebraledema

•  Morehemorrhagicconversion

•  Moredisabilityanddeath

Hyperglycemia

Lindsbergetal.Stroke.2004Feb;35(2):363-4Capesetal.Stroke.2001Oct;32(10):2426-32

ControllingbloodglucoselevelsNICE-SUGARstudy:

•  6,104medical/surgicalICUpatients

•  Randomizedtointensivecontrol(glucose81-108)vs.conventional(glucose<180)

•  Highermortalityinintensivecontrol(27.5vs.24.9%)

•  Moreseverehypoglycemia(<40)inintensivecontrol(6.8vs0.5%)

Hyperglycemia

Finferetal.NEnglJMed.2009Mar26;360(13):1283-97.

StrokeHyperglycemiaInsulinNetworkEffort(SHINE)TrialAcuteischemicstroke,RCTof1400patients

Enrolledwithin12hoursofsymptomonset

Randomizedto•  Insulingtttomaintainglucose80-130forupto72hours

•  Standardcare,i.e.slidingscaleinsulintokeepglucose<180

Outcome:Functionaloutcomeat3months(mRS)

Recentguidelines:Glucose140to180

Morepotentialstrokepatientsoninsulininfusions?

SHINETrial

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79yearoldmale,aphasiaandrightsidedweakness

LKN2hoursprior

NotPAforINR2.3

BP160/90

Glucose120

12hoursafter

admission:

Temperature101.5

Case5

Elevatedtemperatureafterneurologicinjury•  Increasedbrainmetabolicdemand

•  Elevatedlevelsofexcitatoryaminoacids

•  Increasedischemicdepolarizations

•  Blood-brainbarrierbreakdown

•  Impairedfunctionofenzymes

Meta-analysiswith14,431patientswithstrokeandotherbraininjury

Increasedtemperatureassociatedwithworseoutcomes

7measuresincludingclinical,functional,economicoutcome

TemperatureManagement

Greeretal.Stroke.2008Nov;39(11):3029-35.

Typesoftemperaturemanagement:AcetaminophenPharmacologicsedation

Surfacecooling

Endovascularcoolingcatheters

Normothermiavs.HypothermiaHowistemperaturemeasured?Coretemperatures?

Theassumptionthatfeverisharmful

TemperatureManagement

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SmallstudieshaveevaluatedfeasibilityofTTMinstrokePotentialsideeffects:arrhythmias,hypotension,pneumonia

Systematicreview:Noclearbenefitorharm

Shiveringcanbeamajorissue

Increasesmetabolicdemand,potentiallyincreasesICP

HypothermiacanreduceICP

Potentiallydangerousreboundincreasewithmorerewarming

TemperatureManagement

Jauchetal.Stroke.2013Mar;44(3):870-947.Hertogetal.CochraneDatabaseSystRev.2009Jan21

Largenumberofunansweredquestions:Whentostarthypothermia?

Whattargettemperature?Forwhatduration?

Howfasttorewarm?

Whattypeoftemperaturemanagement?(Surface,invasive)

Whichstrokepatients?(e.g.onlylargestrokeswithedema?)

Withothertherapies?(e.g.tPA,angiography,hemicranectomy)

Byitselforwithotherneuroprotectants?

TemperatureManagement

Jauchetal.Stroke.2013Mar;44(3):870-947.

Case664yearoldfemale

SuddenonsetRarmandlegweakness/numbnessIVtPAtreatmentat1.5hours

Diagnosisofnewonsetatrialfibrillation

SymptomsimprovedfollowingtPAAdmittedtoICU

Familymemberasks:“ItakewarfarinforA-Fibtohelppreventstrokes.Shejusthadastroke.Whyisn’tshegettingbloodthinners?”

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Anticoagulation

Jauchetal.Stroke.2013Mar;44(3):870-947

Earlyadministrationofanticoagulantsfollowingstroke?•  Increasedriskofbleeding

Evidencefromclinicaltrials

IncludesbothUFHandLMWH

•  Doesnotlessenriskofearlyneurologicalworsening•  Doesnotlowerriskofearlyrecurrentstroke

Includingcardioembolicstrokes(A-Fib)

Anticoagulation

TheAHAGuidelinesstate:“Dataareinsufficienttoindicatewhetheranticoagulantsmightbeeffectiveamongsomepotentiallyhigh-riskgroups,suchasthosepeoplewithintracardiacorintra-arterialthrombi.”Startinganticoagulantswithin24hoursofIVtPAisnotrecommendedPatientathighriskforfurtherworseningduetoarterialthrombus?

AnticoagulationpotentiallystartedinICUOftenhighleveldecisionwithmuchdiscussion

Anticoagulation

Toanswerthefamilymember’squestion:

Thepatientwillbeplacedonanticoagulation,butnotnow

Currently,theriskofbleedingismorethanthepotentialbenefit

Treatmentshouldbestartedaftertheriskofhemorrhageintothestroketissuehasreduced

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Case778yearoldfemalewithRMCAstroke3daysagoMoredifficulttoarousesincehavingaseizure2hoursagoSeizuretreatedwithLorazepam

Thoughttobesleepysecondarytothis

Withreassessment,slighttwitchingoffacialnoted

Mentalstatusimproveswithfurtherseizuretreatment

PatientismonitoredinICUformoreseizureswithcEEG

Theinternasks,“DidweforgettostartAEDs?”

SeizuresAfterIschemicStrokeIncidencevaries,usuallyreportedin<10%ofischemicstrokesMorecommonwithhemorrhagictransformation

Recurrentseizures?Lateonset?Incidencevariessignificantly

Nodemonstratedbenefitofprophylacticanticonvulsants

Recommendationsbasedonestablishedguidelinesfortreatingseizuresinanyneurologicillness

Advancedmonitoringforseizures(cEEG)intheICUsetting

Jauchetal.Stroke.2013Mar;44(3):870-947Kilinceretal.ActaNeurochir.2005;147:587–594

Case848yearoldmale•  OnsetofRsidedweaknessand

aphasia24hoursago•  TransferredfromOSHforICUcare

•  Concernforedema

•  Neurosurgeryconsultedforhemicraniectomy

Medicalstudentasks:“IhaveseenotherICUpatientswithbrainswellinghavethesecomplicatedmonitorsplaced.Willthispatienthavethatdone?”

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MultimodalMonitoringintheICUIntracranialpressure(ICP)

Braintemperature

Braintissueoxygenation

Jugularvenousoxygensaturation

EEG

Biochemicalmilieuofthebrain

e.g.Microdialysis,testingbrainmicroenvironmentmolecules

Currently,morecommonlyperformedfor:

Traumaticbraininjury

Subarachnoidhemorrhage

AdvancedMonitoring

Risticetal.JNeuroanaesthesiolCritCare2015;2:97-103www.labautopedia.org/

Doesthismonitoringprovidemoreinformationthantheneurologicexamination?

•  Wheretoplacemonitors

•  Focalinjuryvsdiffuse

•  Invasivevsnon-invasivemonitors

•  Similarparameterstootherdiseasestates?e.g.TBI

-PotentialdifferencesinICPandvenousoxygensaturation

Likelymoremonitoringinthefuture

Goalofoptimizingrecoveryandreducingsecondaryinjury

AdvancedMonitoring

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Bloodpressureafterstrokeinvolvescomplicatedphysiology•  CurrentGuidelinesforfirst24hours:

BP<220/120withouttPA,<180/105aftertPA

Selectpatientsmightbenefitfrompressors

LowBPisrare-thinkaboutothercauses

Malignantedemacanoccurafterstroke

•  Potentialtreatmentsincludehemicraniectomy,hypertonicfluid

Hemicrani-lifesavingvs.functionsaving?

Hypertonicsalinevs.mannitol

Summary

Posteriorcirculationstrokecanbedifficulttodiagnosis•  Canresultinobstructivehydrocephalus,herniation,death

•  EVDandsurgicaltreatmentcanbelifesaving

Hyperglycemiaisthoughttobeharmfultobebrainfollowingstroke

•  Isaggressivetreatmenthelpful?Hypoglycemia?

•  Currentguidelines:Maintainglucose140-180

•  LookforresultsofSHINEtrial

Summary

Temperaturemanagementfollowingstrokeisimportant•  Feveristhoughttobebad

•  Limitedevidenceforhypothermiavs.normothermia

•  Hypothermiainstrokepatientshasuniquechallenges

Anticoagulationearlyafterstrokeisnotacommontreatment

•  Selectpatientsmightbenefit

•  Morecommonlypatientsarestartedonanticoagulationlater

Summary

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Seizurescanoccurafterstroke•  cEEGmonitoringcantakeplaceintheICU

•  Treatactualseizuresbasedonestablishedgeneralguidelines

•  Prophylacticanticonvulsantsarenotrecommended

Advancedmultimodalmonitoringhassubstantialpotential

•  Manyunansweredquestionsaboutbestmethods

•  Likelymoreuseinthefuture

Summary

THANKYOU!